TY - JOUR
T1 - TETA analogue containing one methylenephosphonate pendant arm: lanthanide complexes and biological evaluation of its Sm-153 and Ho-166 complexes
AU - Delgado, Rita
N1 - Lima, Luis M. P.
Delgado, Rita
PY - 2010/1/1
Y1 - 2010/1/1
N2 - The thermodynamic stability constants of complexes of 1,4,8,11-tetraazacyclotetradecane-1,4,8-triacetic-11-methylphosphonic acid (H(5)te3a1p) with La3+, Sm3+, Gd3+, Ho3+ and Lu3+ metal ions were determined by potentiometric titrations at 298.2 K and with ionic strength 0.10 M in N(CH3)(4)NO3. The complexes are formed relatively fast and the stability constants exhibited are good although lower than those found for the related ligands H(4)teta and H(8)tetp. At physiological pH the completely deprotonated complex species predominate, unlike what happens with the other mentioned ligands. The Sm-153 and Ho-166 complexes, (153)sm/Ho-166-te3a1p, were synthesised quantitatively at pH 9 and 70 degrees C, and have shown good in vitro stability in human serum and physiological solutions except phosphate buffer (pH 7.4). The in vivo behaviour indicated that both complexes have a similar biological pattern, showing a slow tissue clearance, slow rate of total radioactivity excretion and some in vivo instability, although with some differences in their extend. These results indicate that the replacement of one acetate pendant arm of H4teta by a methylphosphonate one does not provide promising chelators to stabilize radio-lanthanides for in vivo application.
AB - The thermodynamic stability constants of complexes of 1,4,8,11-tetraazacyclotetradecane-1,4,8-triacetic-11-methylphosphonic acid (H(5)te3a1p) with La3+, Sm3+, Gd3+, Ho3+ and Lu3+ metal ions were determined by potentiometric titrations at 298.2 K and with ionic strength 0.10 M in N(CH3)(4)NO3. The complexes are formed relatively fast and the stability constants exhibited are good although lower than those found for the related ligands H(4)teta and H(8)tetp. At physiological pH the completely deprotonated complex species predominate, unlike what happens with the other mentioned ligands. The Sm-153 and Ho-166 complexes, (153)sm/Ho-166-te3a1p, were synthesised quantitatively at pH 9 and 70 degrees C, and have shown good in vitro stability in human serum and physiological solutions except phosphate buffer (pH 7.4). The in vivo behaviour indicated that both complexes have a similar biological pattern, showing a slow tissue clearance, slow rate of total radioactivity excretion and some in vivo instability, although with some differences in their extend. These results indicate that the replacement of one acetate pendant arm of H4teta by a methylphosphonate one does not provide promising chelators to stabilize radio-lanthanides for in vivo application.
KW - ACID ANALOGS
KW - METHYLCARBOXYLATE
KW - MEDICAL APPLICATIONS
KW - AGENTS
KW - TETRAAZAMACROCYCLES
KW - METAL-COMPLEXES
KW - DOTA
KW - THERAPEUTIC RADIOPHARMACEUTICALS
KW - BONE PAIN
KW - CYCLAM DERIVATIVES
U2 - 10.1016/j.ejmech.2010.09.013
DO - 10.1016/j.ejmech.2010.09.013
M3 - Article
VL - 45
SP - 5621
EP - 5627
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 12
ER -